Tube expansion process for semicrystalline polymers to maximize fracture toughness

ABSTRACT

Methods of fabricating a polymeric stent with improved fracture toughness including radial expansion of a polymer tube along its entire length at the same time and fabricating a stent from the expanded tube are disclosed herein.

CROSS REFERENCE TO RELATED APPLICATION

This application claims benefit of U.S. patent application Ser. No.61/086,100, which was filed on Aug. 4, 2008 and claims benefit of andincorporates by reference U.S. patent application Ser. No. 61/095,617,which was filed on Sep. 9, 2008.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to methods of manufacturing polymeric medicaldevices, in particular, stents.

2. Description of the State of the Art

This invention relates to radially expandable endoprostheses, that areadapted to be implanted in a bodily lumen. An “endoprosthesis”corresponds to an artificial device that is placed inside the body. A“lumen” refers to a cavity of a tubular organ such as a blood vessel. Astent is an example of such an endoprosthesis. Stents are generallycylindrically shaped devices that function to hold open and sometimesexpand a segment of a blood vessel or other anatomical lumen such asurinary tracts and bile ducts. Stents are often used in the treatment ofatherosclerotic stenosis in blood vessels. “Stenosis” refers to anarrowing or constriction of a bodily passage or orifice. In suchtreatments, stents reinforce body vessels and prevent restenosisfollowing angioplasty in the vascular system. “Restenosis” refers to thereoccurrence of stenosis in a blood vessel or heart valve after it hasbeen treated (as by balloon angioplasty, stenting, or valvuloplasty)with apparent success.

Stents are typically composed of scaffolding that includes a pattern ornetwork of interconnecting structural elements or struts, formed fromwires, tubes, or sheets of material rolled into a cylindrical shape.This scaffolding gets its name because it physically holds open and, ifdesired, expands the wall of the passageway. Typically, stents arecapable of being compressed or crimped onto a catheter so that they canbe delivered to and deployed at a treatment site.

Delivery includes inserting the stent through small lumens using acatheter and transporting it to the treatment site. Deployment includesexpanding the stent to a larger diameter once it is at the desiredlocation. Mechanical intervention with stents has reduced the rate ofrestenosis as compared to balloon angioplasty. Yet, restenosis remains asignificant problem. When restenosis does occur in the stented segment,its treatment can be challenging, as clinical options are more limitedthan for those lesions that were treated solely with a balloon.

Stents are used not only for mechanical intervention but also asvehicles for providing biological therapy. Biological therapy usesmedicated stents to locally administer a therapeutic substance.Effective concentrations at the treated site require systemic drugadministration which often produces adverse or even toxic side effects.Local delivery is a preferred treatment method because it administerssmaller total medication levels than systemic methods, but concentratesthe drug at a specific site. Local delivery thus produces fewer sideeffects and achieves better results.

A medicated stent may be fabricated by coating the surface of either ametallic or polymeric scaffolding with a polymeric carrier that includesan active or bioactive agent or drug. Polymeric scaffolding may alsoserve as a carrier of an active agent or drug.

The stent must be able to satisfy a number of mechanical requirements.The stent must be capable of withstanding the structural loads, namelyradial compressive forces, imposed on the stent as it supports the wallsof a vessel. Therefore, a stent must possess adequate radial strength.Radial strength describes the external pressure that a stent is able towithstand without incurring clinically significant damage. Additionally,a stent should be sufficiently rigid to adequately maintain its size andshape throughout its service life despite the various forces that maycome to bear on it, including the cyclic loading induced by the beatingheart. For example, a radially directed force may tend to cause a stentto recoil inward. Furthermore, the stent should possess sufficienttoughness or resistance to fracture from stress arising from crimping,expansion, and cyclic loading.

Some treatments with implantable medical devices require the presence ofthe device only for a limited period of time. Once treatment iscomplete, which may include structural tissue support and/or drugdelivery, it may be desirable for the stent to be removed or disappearfrom the treatment location. One way of having a device disappear may beby fabricating the device in whole or in part from materials that erodeor disintegrate through exposure to conditions within the body. Thus,erodible portions of the device can disappear or substantially disappearfrom the implant region after the treatment regimen is completed. Afterthe process of disintegration has been completed, no portion of thedevice, or an erodible portion of the device will remain. In someembodiments, very negligible traces or residue may be left behind.Stents fabricated from biodegradable, bioabsorbable, and/or bioerodablematerials such as bioabsorbable polymers can be designed to completelyerode only after the clinical need for them has ended.

However, there are potential shortcomings in the use of polymers as amaterial for implantable medical devices, such as in, for example, slideand lock stents. There is a need for manufacturing processes or materialmodifications for stents that addresses such shortcomings so that apolymeric stent can better meet the clinical and mechanical requirementsof a stent.

SUMMARY OF THE INVENTION

Various embodiments of the present invention include: a method of makinga stent comprising: heating an axial section of a polymer tube tofacilitate radial deformation of the axial section; radially deformingthe axial section of tube to a target diameter, wherein the axialsection is radially deformed along its entire length at the same time orapproximately the same time; actively cooling the deformed axial sectionto below a target temperature to stabilize the axial section at or closeto the target diameter; and fabricating a stent from the deformed axialsection after the cooling.

Further embodiments of the present invention include: a method of makinga stent comprising: heating an axial section of a polymer tube disposedwithin a cylindrical mold to a deformation temperature, wherein theheating facilitates radial deformation of the axial section within themold; increasing the pressure inside the axial section of the mold to apressure that radially deforms the axial section; allowing the axialsection to radially deform against an inner surface of the mold to adeformed diameter, wherein the axial section is radially deformed alongits entire length at the same time or approximately the same time;cooling the deformed axial section below a target temperature tostabilize the axial section at or close to the deformed diameter; andfabricating a stent from the deformed axial section after the cooling.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a stent.

FIG. 2 depicts a schematic plot of the crystal nucleation rate and thecrystal growth rate for a polymer versus temperature between the Tg andthe Tm under quiescent conditions.

FIGS. 3A-B depict a schematic of an embodiment of the deformation orexpansion process of the present invention.

FIG. 4A depicts a cut-out profile of an exemplary assembly for blowmolding a tube according to the present invention.

FIG. 4B depicts an exemplary split mold design for expanding a polymerictube.

FIG. 5A depicts the components of an aluminum nitride heater.

FIG. 5B depicts an aluminum nitride heater.

FIG. 5C depicts an aluminum nitride heater attached to a heat sinkblock.

FIG. 6 depicts a radial profile of an exemplary mold with cylindricalheater elements embedded in a mold body.

FIG. 7 depicts an ribbon with four notches for hoop strength testing,which was cut from a blow molded tube that was expanded within a moldaccording to blow molding process of the present invention.

FIG. 8 depicts the load-displacement curves of hoop strength testing forribbons shown in FIG. 7.

FIG. 9 depicts a chart showing the measured apparent hoop ultimatetensile strength of test specimens from PLLA tubes expanded usingvarious process conditions.

FIG. 10 depicts a chart showing the measured apparent hoop yield stressof the test specimens of FIG. 9.

FIG. 11 depicts a chart showing the measured maximum radial elongationof the test specimens of FIG. 9.

FIG. 12 depicts the axial elongation at break for the tube samples ofFIG. 9.

FIG. 13 depicts optical micrograph of a blow molded tube 250 that wasexpanded within a mold according to a blow molding process of thepresent invention.

FIG. 14A depicts a close-up view of the optical micrograph of FIG. 13.

FIG. 14B depicts an optical micrograph of a blow molded tube expanded bya method in which the entire tube is not expanded at the same time alongits length.

FIGS. 15A-C illustrates heating of a heat sink with heating fluid andactive and passive cooling of the heat sink.

DETAILED DESCRIPTION OF THE INVENTION

Various embodiments of the present invention relate to manufacture ofpolymeric implantable medical devices, such as stents. In particular,embodiments include methods of expanding a polymer tube and fabricatinga stent therefrom. The methods described herein are generally applicableto any tubular polymeric implantable medical device. In particular, themethods can be applied to tubular implantable medical devices such asself-expandable stents, balloon-expandable stents, and stent-grafts.

A stent may include a pattern or network of interconnecting structuralelements or struts. FIG. 1 depicts a view of a stent 100. In someembodiments, a stent may include a body, backbone, or scaffolding havinga pattern or network of interconnecting structural elements 105. Stent100 may be formed from a tube (not shown). The structural pattern of thedevice can be of virtually any design. The embodiments disclosed hereinare not limited to stents or to the stent pattern illustrated in FIG. 1.The embodiments are easily applicable to other patterns and otherdevices. The variations in the structure of patterns are virtuallyunlimited. A stent such as stent 100 may be fabricated from a tube byforming a pattern with a technique such as laser cutting or chemicaletching.

A stent such as stent 100 may be fabricated from a polymeric tube or asheet by rolling and bonding the sheet to form the tube. A tube or sheetcan be formed by extrusion or injection molding. A stent pattern, suchas the one pictured in FIG. 1, can be formed in a tube or sheet with atechnique such as laser cutting or chemical etching. The stent can thenbe crimped on to a balloon or catheter for delivery into a bodily lumen.

An implantable medical device can be made partially or completely from abiodegradable, bioabsorbable, or biostable polymer. A polymer for use infabricating an implantable medical device can be biostable,bioabsorbable, biodegradable or bioerodable. Biostable refers topolymers that are not biodegradable. The terms biodegradable,bioabsorbable, and bioerodable are used interchangeably and refer topolymers that are capable of being completely degraded and/or erodedwhen exposed to bodily fluids such as blood and can be graduallyresorbed, absorbed, and/or eliminated by the body. The processes ofbreaking down and absorption of the polymer can be caused by, forexample, hydrolysis and metabolic processes.

A stent made from a biodegradable polymer is intended to remain in thebody for a duration of time until its intended function of, for example,maintaining vascular patency and/or drug delivery is accomplished. Afterthe process of degradation, erosion, absorption, and/or resorption hasbeen completed, no portion of the biodegradable stent, or abiodegradable portion of the stent will remain. In some embodiments,very negligible traces or residue may be left behind.

The duration of a treatment period depends on the bodily disorder thatis being treated. In treatments of coronary heart disease involving useof stents in diseased vessels, the duration can be in a range from abouta few months to a few years. However, the duration is typically up toabout six months, twelve months, eighteen months, or two years. In somesituations, the treatment period can extend beyond two years.

As indicated above, a stent has certain mechanical requirements such ashigh radial strength, high modulus, and high fracture toughness. A stentthat meets such requirements greatly facilitates the delivery,deployment, and treatment of a diseased vessel. A polymeric stent withinadequate mechanical properties can result in mechanical failure orrecoil inward after implantation into a vessel.

With respect to radial strength, the strength to weight ratio ofpolymers is usually smaller than that of metals. To compensate for this,a polymeric stent can require significantly thicker struts than ametallic stent, which results in an undesirably large profile.

Additionally, polymers that are sufficiently rigid to support a lumen atconditions within the human body may also have low fracture toughnesssince they may exhibit a brittle fracture mechanism. For example, theseinclude polymers that have a glass transition temperature (Tg) abovehuman body temperature (Tbody), which is approximately 37° C. Suchpolymers may exhibit little or no plastic deformation prior to failure.It is important for a stent to be resistant to fracture throughout therange of use of a stent, i.e., crimping, delivery, deployment, andduring a desired treatment period.

One way of addressing the strength deficiency that a polymer may have isto fabricate a stent from a deformed polymer construct. Deformingpolymers tends to increase the strength and stiffness (i.e., modulus)along the direction of deformation. We have observed that deformationalso tends to increase fracture toughness of polymer constructs andstents. Without being limited by theory, the increased strength andmodulus are due to alignment of polymer chains or a preferred polymerchain orientation along the axis or direction of deformation.

For semicrystalline polymers, the conditions (e.g., time, temperature,stress) of polymer deformation can result in a change in thecrystallinity and crystalline microstructure. The mechanical propertiesof a polymer depend both upon the crystallinity and crystallinemicrostructure. Therefore, it is important to understand the dependenceof these properties on the thermal and deformation history of a polymer.

Generally, in the crystallization of polymers, there are two separateevents that occur. The first event is the formation of nuclei in thepolymer matrix. The second event is growth of the crystallite aroundthese nuclei. The overall rate of crystallization of the polymer isdependent, therefore, on the equilibrium concentration of nuclei in thepolymer matrix, on the exact temperature between Tg (glass transitiontemperature) and Tm (polymer melting temperature), its molecular weight,and on the rate of growth of crystallites around these nuclei.

Semicrystalline polymers can contain both amorphous and crystallinedomains at temperatures below their melting point (Tm). Amorphousregions are those in which polymer chains are in relatively disorderedconfigurations. Crystalline domains or crystallites are those in whichpolymer chains are in ordered configurations with segments of polymerchains essentially parallel to one another.

The classical view of polymer crystallization is a thermodynamically“frustrated” nucleation and growth process. The transition from adisordered state where flexible chains adopt the random coilconformation to a rigid, ordered, three-dimensional state has beenformally treated as a classical first-order transition. Crystallitesform at the stable nuclei and grow by reorganizing random coil chainsinto chain-folded crystalline lamellae (approximately, 10 nm thick).However, individual segments of polymer molecules are often unable toadopt the thermodynamically desirable conformation state necessary forcrystallization before adjacent segments crystallize, locking innon-equilibrium amorphous structure. Thus, semicrystalline polymers forma mixture of ordered crystalline and disordered amorphous regions. Thecrystalline lamellae form sheaf-like stacks a few lamellae thick(approximately 50 to 100 nm) that splay and branch as they grow outward,forming spherulites varying from submicron to millimeters in size. Thegrowth of an individual spherulite ceases when it impinges withneighboring spherulites. Only in the theoretical limit of infinite timeat the equilibrium melting temperature could a semicrystalline polymerform the thermodynamic ideal single-crystal structure. Even at infinitetime, there will be some defects in the semi-crystalline structure, suchas the chain ends. So one can get close, but not 100% idealsingle-crystal structure. The fastest approach to near ideal, which doesnot require long times, is to grow the crystal from dilute solutions.

Although the crystal structure described above is very common, theultimate semi-crystalline structure will depend upon processingconditions. Another semi-crystalline structure is one in which thepolymer is processed so that the chains are preferentially oriented in aprocessing direction. This structure will have no or very fewspherulites and relatively few chain folds.

Hence, for all practical situations, semicrystalline polymers assume akinetically-driven, non-equilibrium morphology in the solid state. Theoverall crystallization kinetics follows the general mathematicalformulation that has been developed for the kinetics of phase changeswith only minor modifications. The importance of nucleation processes inpolymer crystallization has been amply recognized. This concept has beenapplied to the analysis of the kinetics of polymer crystallization.

In general, the crystallization process occurs in a polymer attemperatures between Tg and Tm of the polymer. FIG. 2 shows a schematicof the dependence of nucleation rate (A) and crystal growth rate (B) ontemperature between the Tg and the Tm under quiescent conditions, i.e.,in the absence of deformation to the polymer. At temperatures above Tgbut far below Tm where polymer chain mobility is limited, nucleation issubstantially favored over growth, since the latter process requiresmuch more extensive chain mobility. These nuclei remain present in thepolymer until its temperature is elevated above Tm for a period of time.A consequence of the behavior illustrated in FIG. 2 is that at hightemperatures below Tm there are relatively few, large crystallitesformed, while at low temperatures, there are relatively more numerous,smaller crystallites formed.

Most semicrystalline polymers crystallize slowly from the quiescentstate, but orders of magnitude faster when the material is subjected todeformation. These deformations are characteristic of processing abovethe Tg, but below the Tm. Such crystallization is referred to in physicsas strain-induced (or flow-induced) crystallization. Liedauer, et al.,Int. Polym Proc. 8, 236-244(1993); Kumaraswamy, et al, Macromolecules35, 1762-1769(2002).

Poly (L-lactic acid) (PLLA) is but one example of the class ofsemicrystalline polymers for which the above description is true. When atubular PLLA preform (e.g., extruded, dip coated, or injection moldedtube) is radially expanded, axially (referring to the cylindrical axisof the tube) elongated, the material can become highly crystalline(e.g., greater than 50% as measured by differential scanningcalorimetry). The polymer can concomitantly become brittle if allowed toreside above its Tg sufficiently long. Thus, these highly crystallineparts (e.g., stents) can suffer from a brittle fracture mechanism uponcrimping and/or deployment.

The above discussion indicates that polymer microstructure, and thus,mechanical properties are directly related to the thermal anddeformation history of a polymer. Specifically, the thermal historyincludes the magnitude of the temperature before, during, and afterdeformation of a polymer construct. The thermal history also includesthe temporal temperature profile or the temperature versus time before,during and after deformation. The microstructure and mechanicalproperties of a polymer construct following a deformation process canvary dramatically as the thermal history is altered.

In particular, we expect the fracture toughness of a polymer to dependon the thermal and deformation history if the polymer. Fracturetoughness tends to be directly proportional to crystallite density andinversely proportional to crystallite size. As a result, fracturetoughness is particularly enhanced or improved when a polymer has arelatively high crystallite density with crystallites that arerelatively small in size. Additionally, the degree of crystallinity andcrystalline and amorphous orientation also affects the fracturetoughness. As mentioned already, a crystallinity that is too high canresult in an undesirable decrease in fracture toughness and brittlebehavior.

Thus, since nucleation rate is faster than crystallite growth rate atlower temperature close to Tg, it is preferable for the temperature ofthe tube be in this range during deformation. The crystallinity obtaineddepends upon the magnitude of the temperature and the time that the tubeis in the crystallization temperature range, i.e., between Tg and Tm.

Another important property of a polymer construct for medical devicefabrication is spatial uniformity of mechanical properties of theconstruct. Specifically for a tube, spatial uniformity may refer touniformity of properties along the length of the tube and around thecircumference. Spatial uniformity is important generally for mechanicalstability and, generally, the performance of a device. Due to thedependence of mechanical properties on thermal and deformation historyin general, it follows that the spatial thermal deformation history(e.g., time and temperature history along the length of a tube) willinfluence the spatial uniformity of the mechanical properties.Therefore, to fabricate an expanded tube with superior fracturetoughness and performance, it is of paramount importance to control itsthermal and deformation history.

Embodiments of the present invention described below include deformationof a polymer tube in which the thermal and deformation history arecontrolled to enhance the fracture toughness of the expanded tube.Additionally, the embodiments include controlling the degree ofuniformity of the thermal and deformation history to enhance uniformityof the mechanical properties of the polymer tube. Deformation can referradial expansion and axial elongation of the tube. The radial expansioncan be accomplished by a blow molding process. The embodiments furtherinclude making a stent from radially expanded tube which has superiorfracture toughness and spatial uniformity of mechanical properties.

Generally, the embodiments of the fabrication method include heating apolymer tube above an ambient temperature to facilitate or allowdeformation, deforming the heated tube, and cooling the deformed sheetto stabilize the changed microstructure of the polymer structure.

The changed microstructure includes crystal structure and inducedpolymer chain orientation. More particularly, various embodiments of thepresent invention include heating an axial section of a polymer tube tofacilitate radial deformation of the axial section. The axial section issufficiently long to fabricate at least one stent. The axial section canbe heated from an initial temperature, for example ambient temperature(T ambient) to a target deformation temperature between Tg and Tm of thepolymer. The heated axial section is radially deformed to a targetdiameter.

The polymer tube can be composed 100% of a homopolymer or blend ofpolymers or consist essentially of a copolymer or blend of polymersincluding copolymers. The polymer tube can be composed of a polymer orpolymers with non-polymer substances, such as metallic or ceramicparticles, dispersed or mixed within a polymer.

In embodiments of the invention, the radial deformation is performed tofacilitate expansion along the whole length of the axial section at thesame time. In these embodiments, the axial section is radially deformedalong its entire length at the same time or approximately the same time.

After radial expansion, the expanded axial section is actively cooled tobelow a target temperature to stabilize the axial section at or close tothe target diameter. The target temperature can be, for example, Tg or Tambient. Subsequent to cooling, a stent can be fabricated from theentire axial section or at least a portion of the deformed axialsection.

In certain embodiments, the tube is made of a semicrystalline polymerwith a Tg above Tbody. In order to facilitate stability of the stent atconditions within a human body, the Tg may be at least 10, 20, or 30° C.greater than Tbody.

As indicated, the radial expansion of the tube can be achieved through ablow molding process. Blow molding generally refers to a process inwhich a polymeric tube is placed in a tubular mold and deformed in theradial direction through an increase in the pressure inside the tube byblowing a gas into the tube. The increased pressure expands the tube andthe mold limits the radial deformation of the polymeric tube to theinside diameter of mold. To facilitate expansion, the tube made of asemicrystalline polymer is typically heated to a temperature above Tg,but below Tm.

The control of the thermal and deformation history in a tube expansionprocess, such as blow molding, that provides enhanced fracture toughnessand spatial uniformity includes, but is not limited to (1) rapidlyheating the tube above Tg (and below Tm); (2) expanding the entire tubeat one time or the same time; and (3) rapidly cooling or quenching thetube below Tg. Such control allows superior control over the materialmicrostructure, including both crystalline and amorphous orientationstates, crystalline lamellar thickness and spacing, overall degree ofcrystallinity (χ_(c)), microstructural homogeneity along the tube axis,and ultimately tunable macroscopic material properties, includingfracture toughness.

FIGS. 3A-B depict a schematic of an embodiment of the deformation orexpansion process of the present invention. The expansion process is notlimited to that disclosed and can be accomplished in a variety of ways,not exclusively as disclosed herein. FIG. 3A depicts an axialcross-section of a polymeric tube 150 with an outside diameter 155positioned within a mold 160. Mold 160 has a mold body 162 with atubular cavity 163 that is tapered at its distal and proximal ends. Achuck 152 holds at least one end of tube 150. When polymeric tube 150expands, mold 160 limits its radial deformation to a diameter 165, thediameter of tubular cavity 163. Polymer tube 150 may be closed at adistal end 170. Distal end 170 may be open in subsequent manufacturingsteps.

Prior to expansion, polymeric tube 150 is heated to increase itstemperature to make the tube ductile and amenable to expansion. Atemperature at which the polymeric tube is deformed or deformationtemperature is between Tg and Tm of the polymer. The tube is heated tofacilitate or provide a uniform temperature along the length of the tubeand around the circumference of the tube. The tube can be heated in anumber of ways, which are discussed in more detail below. For example, anozzle or nozzles can heat the tube by directing a warm gas on mold 160,as shown by arrows 182, along the length of mold body 162 that includestubular cavity 163.

When the polymeric tube is heated to a deformation temperature, thepressure is increased inside the tube to a deformation pressure toradially deform the tube. A fluid is conveyed, as indicated by an arrow175, into proximal end 180 of polymeric tube 150 to increase thepressure inside of the tube. A tensile force 195 can be applied atdistal end 170 to axially deform tube 150. Tension can also be appliedat both ends.

The increase in pressure inside of polymer tube 150 facilitated by theincrease in temperature of the polymeric tube causes radial deformationof an axial section of polymeric tube 150 contained within tubularcavity 163. The axial section is radially deformed along its entirelength at the same time or approximately the same time, as indicated byarrows 185. FIG. 3B depicts polymeric tube 150 with an axial section 187in a deformed state with an outside diameter 190.

In order to stabilize the deformed state, the tube is then cooled,preferably to below the Tg of the polymer. The tube is preferably cooledto obtain a uniform or relatively uniform decrease in temperature alongthe length and circumference of the tube. The tube can be cooled in anumber of ways, which are discussed in more detail below. For example,cooled gas can be directed at mold 160 along all or most of the lengthof the tube, as shown by arrows 192.

There are various processing variables of the radial deformationprocess, in particular, the blow molding process, which may influencethe fracture toughness and other properties of a deformed tube. Theseinclude the deformation temperature, the time the tube is heated untilit is deformed at the deformation temperature (heating time), the timedelay between the deformation of the tube (when the tube is deformedagainst inner surface of the mold) and the start of active cooling(cooling delay), and the duration of active cooling of the tube (activecooling time), and the time for the active cooling to cool the tube tobelow Tg (Tg cooling time). The time at which the tube is deformed cancorrespond to the time at which the tube conforms completely orsubstantially to the inside surface of the mold. Substantially deformedmay correspond to a deformed tube with air bubbles between the tube walland the mold. In a typical embodiment, the active cooling time may behigher than the Tg cooling time.

“Active cooling” refers to cooling the tube through exposure of the tubeand/or mold to conditions below ambient temperature that results in adecrease in temperature of the tube. Passive cooling includes allowingthe tube to cool only through the exposure of the tube and mold toambient conditions. During the cooling delay, the tube may be cooledpassively or experience a decrease in temperature through exposure ofthe mold and tube to ambient temperature or above ambient temperature.Alternatively, heating of the mold and tube may continue during some orall of the cooling delay.

The fracture toughness of a deformed tube is believed to be dependentupon the parameters of deformation temperature, heating time, coolingdelay, Tg cooling time, and the active cooling time. The parameters maybe adjusted to obtain a desired or optimum fracture toughness, modulus,and radial strength of the deformed tube. In some embodiments, values ofthe parameters that achieve a high fracture toughness may be determinedby measuring and evaluating properties related to fracture toughness forvarious values of the parameters. For example, the elongation at breakof tube specimens or the number of cracks in a stent made from the tubeafter deployment can be measured for various values of the parameters.

The deformation temperature refers to the temperature of the tube whenit is radially deformed. A higher fracture toughness for asemicrystalline polymer may be achieved by a relatively low deformationtemperature, for example, a temperature that is above and close to Tg.In exemplary embodiments, a deformation temperature can be 2° C., 2-5°C., 5-10° C. , 5-45° C., or greater than 45° C. above a Tg of thepolymer example, the deformation temperature can be 5-10° C., 5-30° C.,or 5-45° C. above a Tg of the polymer of the tube.

In addition to being near and above Tg, actual preferred temperaturesthat yield desirable properties (e.g., high strength, high modulus,and/or high fracture toughness) will depend upon extruded tube wallthickness and molecular weight. For example, for PLLA, temperatureranges between 70 and 110° C. have yielded useful and desirableproperties. Temperatures between 79 and 93° C. are particularlypreferred for the extruded tubes with the particular grade of PLLA usedby the inventors. In addition, in some embodiments, a higher fracturetoughness may be achieved by a rapid heating time, short cooling delay,and fast Tg cooling time.

In a blow molding apparatus, the temperature of the mold can be measuredby a temperature sensor disposed in the mold wall or on the inside oroutside surface of the mold. It is expected that a temperaturedifferential can exist between the measured temperature and the tubetemperature. Such differential may be less than 0.5, 1, 2, or greaterthan 2° C.

As indicated above, a relatively rapid heating time facilitates a highfracture toughness. It is believed that the rapid heating time reducesthe amount of time the tube temperature is in a crystallization range inwhich nucleation and growth occurs. It also creates crystalline andamorphous orientation that has no time to relax as it would if heatingis too slow. The relaxation refers only to the amorphous orientation andin addition, the subsequent cooling below Tg must also not be too slow.If the heating is too slow, the increase in crystallinity from theheating coupled with the strain-induced crystallization from thedeformation can result in a tube that is brittle with low fracturetoughness.

Typically, the polymer tube is heated from Tambient. In exemplaryembodiments, a PLLA polymer sheet is heated from Tambient to adeformation temperature in less than 5 s, between 5-10 s, between 10-20s, between 20-35 s, 35-50 s, or greater than 50 s.

In certain embodiments, the cooling delay is reduced or minimized toreduce or eliminate a further increase crystallinity after deformationand to stabilize or freeze the induced polymer chain orientation. Insome embodiments, the cooling of the deformed tube starts immediately orslightly after (less than 1 sec) the tube has completed deformation. Inother embodiments, a cooling delay is selected to allow a furtherincrease in crystallinity that improves mechanical properties. Also, acooling delay help may relieve internal stress in the polymer whichresults in dimensional instability (i.e., a distortion in tubularshape). A cooling delay may also provide time for air pockets or bubblesbetween the outer surface of tube and inner surface of the mold todissipate or disappear. An exemplary cooling delay may be less than 2 s,5 s, 10 s, or greater than 10 s.

In some embodiments, the cooling delay may be controlled by a tensionsensor that senses the tension in the tube radially or axially. In thisembodiment, the cooling may be activated when a desired tension isachieved.

Additionally, achieving a high fracture toughness may be facilitated byrapid cooling from the deformation temperature to a temperature belowthe Tg of the polymer. A rapid cooling time minimizes an additionalincrease in crystallinity that can occur while the tube is above the Tgof the polymer. In such embodiments, the deformed tube is activelycooled. Various ways of active cooling are described below. Exemplarycooling times to cool a deformed tube from the deformation temperatureto a Tg or Tambient are less than 0.5 sec, 1 sec, 5 sec, or greater than10 s.

The active cooling time is selected to be sufficient to reduce thedeformed tube temperature below the polymer Tg, i.e., the Tg coolingtime. Exemplary, Tg cooling times can be less than 2 s, 2-5 s, 5-10 s,or greater than 10 s.

Additionally, the heating and cooling are preferably performed tofacilitate or provide uniform or substantially or uniform temperatureprofiles axially and circumferentially in the tube. Such uniform heatingand cooling provides a spatially uniform temperature history whichfacilitates uniform mechanical properties. Such uniform heating alsoprovides for uniform deformation, also facilitating spatially uniformmechanical properties.

As indicated above, the tube may be elongated by a tensile force. Thetensile force may be constant or variable with time. In an embodiment,the tensile force may be constant or the tensile force can be adjustedto provide a constant strain rate. The tube may be heated to thedeformation temperature prior to applying a tension that elongates thetube. Additionally, the tube may be elongated prior to deformation,during deformation, after deformation, or a combination thereof.

In further embodiments, the tube can be annealed prior to deformation toincrease the nucleation density prior to expansion to decrease thecrystal size in the final product. In such an annealing process, thetube can be heated to a temperature that allows the formation of nuclei,but allows no or substantially no crystal growth. The temperature ofannealing can be between a temperature of Tg and Tg+20° C. After theannealing step, the tube can be deformed or heated further to adeformation temperature and then deformed.

Several heating methods include applying or directing heat to the moldto heat the tube. In such embodiments, a mold can be made from amaterial with a high thermal conductivity which facilitates uniformheating in the axial and circumferential directions as well as allowingfor rapid heating and cooling of the tube. In general, the mold may bemade of a material having a thermal conductivity greater than 50 W/m K.In particular, the mold may be made of a metal or partially of a metal.For example, the mold may be made of aluminum, stainless steel, brass,or a Be—Cu alloy. In additional embodiments, the mold may be made of aporous material to reduce or prevent gas entrapment between the innersurface of the mold and outer surface of an expanded tube, therebyimproving dimensional control. For example, the mold inner surface mayhave micron-size pores (e.g., 1-100 microns) through which gas canescape.

As discussed above, there are several mechanisms and methods of heatingthe tube during the blow molding process described above. Exemplaryheating methods include radiant, heated gas, resistive, thermoelectric,or conductive.

As discussed above, the tube may also be heated by directing a heatedgas onto the mold. For example, an elongated nozzle or a series ofnozzles can be positioned along the tube axis at one or morecircumferential positions. The nozzle or nozzles direct heated gas ontothe mold which heats the tube. Due to the high thermal conductivity ofthe mold and the flow of the gas around the tube, the directed gas canheat the mold, and thus, the tube relatively uniformly axially andcircumferentially. Alternatively, a nozzle directs heated gas at only aportion of an axial section of the tube can rapidly translate axiallyalong the tube to heat the tube uniformly along its length.

Additionally, or alternatively to other heating methods, the compressedgas directed into the tube for expansion may also be at a temperature ofTambient. The gas may include air, nitrogen, argon, or other inertgases. In particular, compressed helium may be used. Helium has athermal conductivity at 25° C. that is almost 6 times that of air ornitrogen and almost 9 times that of argon. The higher thermalconductivity may result in faster and more uniform heating of the tube.

Radiant heating can include, for example, infrared heating. To obtainuniform heating of the tube, several infrared sources or an elongatedinfrared source may be positioned along the mold axis at one or morecircumferential positions. Infrared heating can be adjusted so only theextruded tube is heated while the mold, if made of glass, is kept cold.That way expansion can occur against a cold mold, where cold may referto a temperature near or at Tambient or below Tambient.

An electrical resistance heater may be positioned on, within, oradjacent to the mold to heat the tube. Alternatively, electricalresistive heating elements can be embedded in the mold. For example,electrical resistive heating elements can be distributed around andalong the mold to provide uniform heating of the mold and tube.

Thermoelectric, in particular Peltier devices, may be used to heat themold and balloon. Peltier devices refer to solid-state devices thatfunction as heat pumps. A typical Peltier unit is a sandwich formed bytwo ceramic plates with an array of small Bismuth Telluride or othermaterial cubes in between. When a DC current is applied, heat is movedfrom one side of the device to the other. The Peltier device can bepositioned so that the heated side is adjacent to the mold. When currentis reversed, the direction of heat transfer is reversed and the deviceacts a cooler to cool the mold after expansion. The heat can be removedby a heat sink.

Various methods may be used for cooling the mold and the deformed tube.A chilled fluid, such as water, may be circulated within or adjacent tothe mold. For example, the mold can include channels or cavities throughwhich the chilled fluid can circulate. The channels may be distributedaround the circumference of the mold and along its length to provideuniform cooling.

Alternatively or additionally, a chilled gas may be used for cooling.Some embodiments can include directing a chilled gas onto the outsidesurface of the mold in the manner described for heating the mold withnozzles directing heated gas. A chilled gas may additionally oralternatively be directed into the expanded tube. The chilled gas may beat atmospheric pressure or compressed, for example, at a pressurebetween atmospheric and the deformation pressure.

Additionally, as discussed above, a heat sink can be used for cooling.The heat sink can be used in conjunction with a thermoelectric heater asdescribed above. Alternatively, the heat sink can be positioned adjacentto the mold. The heater is placed between the heat sink and the mold.Materials that connect the mold to the heater and the heater to the heatsink in some embodiments are selected to increase resistance or decreaseresistance of heat or cooling flow. An optimized combination of materialselection can increase the speed and the accuracy of the active heatingand active cooling that is desired to produce optimum materialproperties.

A split mold design may be used in some embodiments to further increasespeed of heating and cooling and facilitate the ease of manufacturing. Asplit mold allows two heaters thus faster cooling and heating for halfthe mass of a given mold. Another advantage is it allows the tube to beloaded and unloaded quickly.

In other embodiments, a mold can be positioned between a heating mediumand a cooling medium, for example, a heating plate and a cooling plate.The mold can be coupled to motion system that can translate the moldbetween the heating plate and the cooling plate. During heating, themold can be positioned adjacent to or in contact with the heating plate.When heating is completed, the mold can be translated to adjacent to orin contact with the cooling plate to rapidly cool the mold.

In some embodiments, the inside surface of the mold can have a layer ofa material reduce or eliminate sticking of the expanded tubing. Forexample, the inside surface can have layer of a non-stick polymer suchas polytetrafluoroethylene or polytetrafluoroethene (PTFE) which isknown by the brand name Teflon®.

FIG. 4A depicts a cut-out profile of an exemplary assembly 200 for blowmolding a tube according to the present invention. Assembly 200 has amold body 207 in to which tube (not shown) can be disposed along itlongitudinal axis. Mold body 207 is held between a lower mold housing208A and an upper mold housing 208B. Mold body 207 is removable from theupper and lower mold housing. Mold body 207 has a cylindrical moldcavity 206 with tapered ends. A tube that extends along the axis of moldcavity 206 initially has a diameter less than mold cavity 206. Duringthe blow molding process, the tube expands to the diameter of moldcavity 206 so that the outside surface of the tube is against the insidesurface of mold cavity 206. A sheet heater 204 is disposed below lowermold housing 208A. Sheet heater 204 is below the whole length of moldcavity 206 to uniformly heat a whole length of an axial section of tubedisposed in mold cavity 206. A low resistance gap pad is positionedbetween lower mold housing 208A and sheet heater 204. A heat sink 202,which may be water-cooled, is positioned below sheet heater 204. A highresistance gap pad 212 and a conductive epoxy bond 214 are positionedbetween sheet heater 204 and heat sink 202.

In some embodiments, active cooling of the heat sink with a chilledfluid corresponds to increasing and decreasing cooling water to the heatsink at the appropriate time to enhance the heating and cooling speed.For instance, a decrease cooling water flow during heat up and increasein cooling water flow during cool down. The greater the difference intemperature, the faster the rates.

FIG. 4B depicts an exemplary split mold design for expanding a polymerictube which shows a half mold member 216A and half mold member 216B. Halfmold member 216A has a half-cylindrical shaped cavity 217 and half moldmember 216B has a corresponding cavity (not shown). When half moldmembers 216A and 216B are positioned together as shown by arrows 218,the cavities form a mold into which a tube expands during blow molding.

Sheet heater 204 can be a ceramic heater, such as an aluminum nitride(ALN) heater, which can be obtained from Delta Design of Poway, Calif.FIG. 5A depicts the components of an aluminum nitride heater whichincludes layers of ALN sheets 220, RTD trace sheets 222, and heatertrace sheets 224. An aluminum nitride heater 226, shown in FIG. 5C, isattached to heat sink block 228, as shown in FIG. 5C. Heat sink block228 is always cold, while the aluminum nitride heater faces and heatsthe mold, as shown in FIG. 4A. As soon as the heater is turned off,cooling occurs very efficiently since the heater has little thermalmass.

FIG. 6 depicts a radial profile of an exemplary mold 240 for blowmolding a tube according to the present invention. Mold 240 has a moldbody 242 with a tubular mold cavity 244 within which a tube (not shown)is expanded against inner wall 245 of mold body 242. Elongated heaters246 are embedded in mold body 242 for heating the mold and tubepositioned within mold cavity 244. Heaters 246 may be tubular resistivecartridge heating elements that are inserted holes drilled into moldcavity 244. Heaters 246 are distributed radially within the wall of moldbody 242 and extend along the axis of mold body 242 at least along thelength including mold cavity 244. Additionally, mold body 242 includes athermocouple 248 for monitoring the temperature of the mold during theblow molding process. Thermocouple 248 can extend along partially orcompletely along the axis of mold body 242 so that it can monitor thetemperature along part of or the entire mold body 242 adjacent to moldcavity 244.

The degree of radial deformation may be quantified by percent radialexpansion:

$\left\lbrack {\frac{{Outside}\mspace{14mu}{Diameter}\mspace{14mu}{of}\mspace{14mu}{Deformed}\mspace{14mu}{Tube}}{{Original}\mspace{14mu}{outside}\mspace{14mu}{Diameter}\mspace{14mu}{of}\mspace{14mu}{Tube}} - 1} \right\rbrack \times 100\%$

In some embodiments, percent radial expansion can be 200-500%. In anexemplary embodiment, the percent radial expansion is about 300%.Similarly, the degree of axial deformation may be quantified by thepercent axial elongation:

$\left\lbrack {\frac{{Length}\mspace{14mu}{of}\mspace{14mu}{Deformed}\mspace{14mu}{Tube}}{{Original}\mspace{14mu}{Length}\mspace{14mu}{of}\mspace{14mu}{Tube}} - 1} \right\rbrack \times 100\%$The percent axial elongation can be, for example, 0-200%.

Axial polymer orientation is also imparted to a tube during formation ofthe tube as the polymer is drawn out of a die during the extrusionprocess. The degree of axial orientation of polymer provided by the drawdown process is related the axial drawn down ratio:

$\frac{{Inside}\mspace{14mu}{Diameter}\mspace{14mu}{of}\mspace{14mu}{Die}}{{{Original}\mspace{14mu}{Inside}\mspace{14mu}{Diameter}\mspace{14mu}{of}\mspace{14mu}{Tube}}\;}.$In an exemplary embodiment the axial drawn down ratio is 2:1 to 6:1.

For the purposes of the present invention, the following terms anddefinitions apply:

“Ambient temperature” can be any temperature including and between 20°C. and 30° C.

The “glass transition temperature,” Tg, is the temperature at which theamorphous domains of a polymer change from a brittle vitreous state to asolid deformable or ductile state at atmospheric pressure. In otherwords, the Tg corresponds to the temperature where the onset ofsegmental motion in the chains of the polymer occurs. When an amorphousor semicrystalline polymer is exposed to an increasing temperature, thecoefficient of expansion and the heat capacity of the polymer bothincrease as the temperature is raised, indicating increased molecularmotion. As the temperature is raised the actual molecular volume in thesample remains constant, and so a higher coefficient of expansion pointsto an increase in free volume associated with the system and thereforeincreased freedom for the molecules to move. The increasing heatcapacity corresponds to an increase in heat dissipation throughmovement. Tg of a given polymer can be dependent on the heating rate andcan be influenced by the thermal history of the polymer. Furthermore,the chemical structure of the polymer heavily influences the glasstransition by affecting mobility.

“Stress” refers to force per unit area, as in the force acting through asmall area within a plane. Stress can be divided into components, normaland parallel to the plane, called normal stress and shear stress,respectively. Tensile stress, for example, is a normal component ofstress applied that leads to expansion (increase in length). Inaddition, compressive stress is a normal component of stress applied tomaterials resulting in their compaction (decrease in length). Stress mayresult in deformation of a material, which refers to a change in length.“Expansion” or “compression” may be defined as the increase or decreasein length of a sample of material when the sample is subjected tostress.

“Strain” refers to the amount of expansion or compression that occurs ina material at a given stress or load. Strain may be expressed as afraction or percentage of the original length, i.e., the change inlength divided by the original length. Strain, therefore, is positivefor expansion and negative for compression.

“Strength” refers to the maximum stress along an axis which a materialwill withstand prior to fracture. The ultimate strength is calculatedfrom the maximum load applied during the test divided by the originalcross-sectional area.

“Modulus” may be defined as the ratio of a component of stress or forceper unit area applied to a material divided by the strain along an axisof applied force that results from the applied force. For example, amaterial has both a tensile and a compressive modulus.

The tensile stress on a material may be increased until it reaches a“tensile strength” which refers to the maximum tensile stress which amaterial will withstand prior to fracture. The ultimate tensile strengthis calculated from the maximum load applied during a test divided by theoriginal cross-sectional area. Similarly, “compressive strength” is thecapacity of a material to withstand axially directed pushing forces.When the limit of compressive strength is reached, a material iscrushed.

“Toughness” is the amount of energy absorbed prior to fracture, orequivalently, the amount of work required to fracture a material. Onemeasure of toughness is the area under a stress-strain curve from zerostrain to the strain at fracture. The units of toughness in this caseare in energy per unit volume of material. See, e.g., L. H. Van Vlack,“Elements of Materials Science and Engineering,” pp. 270-271,Addison-Wesley (Reading, Pa., 1989).

The underlying structure or substrate of an implantable medical device,such as a stent can be completely or at least in part made from abiodegradable polymer or combination of biodegradable polymers, abiostable polymer or combination of biostable polymers, or a combinationof biodegradable and biostable polymers. Additionally, a polymer-basedcoating for a surface of a device can be a biodegradable polymer orcombination of biodegradable polymers, a biostable polymer orcombination of biostable polymers, or a combination of biodegradable andbiostable polymers.

It is understood that after the process of degradation, erosion,absorption, and/or resorption has been completed, no part of the stentwill remain or in the case of coating applications on a biostablescaffolding, no polymer will remain on the device. In some embodiments,very negligible traces or residue may be left behind. For stents madefrom a biodegradable polymer, the stent is intended to remain in thebody for a duration of time until its intended function of, for example,maintaining vascular patency and/or drug delivery is accomplished.

Representative examples of polymers that may be used to fabricate animplantable medical device include, but are not limited to,poly(N-acetylglucosamine) (Chitin), Chitosan, poly(hydroxyvalerate),poly(lactide-co-glycolide), poly(hydroxybutyrate),poly(hydroxybutyrate-co-valerate), polyorthoester, polyanhydride,poly(glycolic acid), poly(glycolide), poly(L-lactic acid),poly(L-lactide), poly(D,L-lactic acid), poly(D,L-lactide),poly(caprolactone), poly(trimethylene carbonate), polyester amide,poly(glycolic acid-co-trimethylene carbonate), co-poly(ether-esters)(e.g. PEO/PLA), polyphosphazenes, biomolecules (such as fibrin,fibrinogen, cellulose, starch, collagen and hyaluronic acid),polyurethanes, silicones, polyesters, polyolefins, polyisobutylene andethylene-alphaolefin copolymers, acrylic polymers and copolymers otherthan polyacrylates, vinyl halide polymers and copolymers (such aspolyvinyl chloride), polyvinyl ethers (such as polyvinyl methyl ether),polyvinylidene halides (such as polyvinylidene chloride),polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such aspolystyrene), polyvinyl esters (such as polyvinyl acetate),acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides,polyethers, polyurethanes, rayon, rayon-triacetate, cellulose, celluloseacetate, cellulose butyrate, cellulose acetate butyrate, cellophane,cellulose nitrate, cellulose propionate, cellulose ethers, andcarboxymethyl cellulose. Another type of polymer based on poly(lacticacid) that can be used includes graft copolymers, and block copolymers,such as AB block-copolymers (“diblock-copolymers”) or ABAblock-copolymers (“triblock-copolymers”), or mixtures thereof.

Additional representative examples of polymers that may be especiallywell suited for use in fabricating or coating an implantable medicaldevice include ethylene vinyl alcohol copolymer (commonly known by thegeneric name EVOH or by the trade name EVAL), poly(butyl methacrylate),poly(vinylidene fluoride-co-hexafluororpropene) (e.g., SOLEF 21508,available from Solvay Solexis PVDF, Thorofare, N.J.), polyvinylidenefluoride (otherwise known as KYNAR, available from ATOFINA Chemicals,Philadelphia, Pa.), ethylene-vinyl acetate copolymers, and polyethyleneglycol.

EXAMPLES

PLLA polymeric tubes were radially expanded by a method of the presentinvention. The tubes were extruded PLLA tubes with an inside diameter(ID) of 0.060 inches and an outside diameter (OD) of 0.084 inches. Thetubes were disposed in a metallic mold having an inside diameter of0.136 inches. The mold was heated by a nozzle that blew hot air alongthe entire length of the mold so that a tube in the mold expanded alongthe entire length of the mold at the same time. The pressure inside thetube was increased by blowing room temperature air into the tube.

Tubes were expanded using 21 different processing conditions which arelisted in Table 1. At least 5 expanded tubes were generated for eachprocessing condition. The air temperature from the heated nozzle isshown in the second column of Table 1 in degrees Fahrenheit. After thetube is expanded, the tube is cooled by a nozzle blowing cooled air onthe outside surface of the mold. The air flow rate directed into thetube is also given in column 2 of Table 1 in scfh (cubic feet per hourof gas flow at standard conditions of temperature and pressure, i.e., 0°C. and 100 kPa). The cooling delay, cooling time, and the process timein seconds are given in column 3. The cooling delay is the time delaybetween the deformation or expansion of the tube against the innersurface of the mold and the start of cooling. The start of coolingcorresponds to the start of the blowing of the cooled air on the mold.The cooling time is the length of time the cooled air is blowing on themold. The process time is the total process time which includes theheating time, cooling delay, and the cooling time. The cooling time doesnot necessarily correspond to the time the tube takes to go from theexpansion temperature to the Tg of the polymer tube. It is expected thatthe tube reaches the Tg of the polymer at a time much less than thecooling time, e.g., in less than 50% or 25% of the cooling time.

TABLE 1 Process conditions for expanson of PLLA tubes. Air flow rate was90 scfh for each set of conditions. Process Expansion Condition Airtemperature Cooling delay/cooling Pressure Identifier (degrees F. andC.) time/process time (psi) 1 175 65.2  2 s/15 s, 56 s 244 2 175 65.2 2s/15 s, 46 s 256 3 175 65.2  2 s/14 s, 52 s 244 4 175 65.2  1 s/14 s,52 s 244 5 175 65.2  5 s/15 s, 47 s 244 6 165 59.7  1 s/10 s, 57 s 256 7222 91.3 10 s/15 s, 30 s 256 8 205 81.9 10 s/15 s, 42 s 256 9 200 79.1 3 s/10 s, 50 s 276 10 200 79.1  8 s/12 s, 38 s 256 11 195 76.3 10 s/12s, 46 s 256 12 170 62.4  1 s/10 s, 65 s 246 13 170 62.4  1 s/10 s, 61 s246 14 170 62.4  1 s/10 s, 61 s 246 15 200 79.1  6 s/15 s, 46 s 256 16190 73.6  3 s/12 s, 45 s 256 17 190 73.6  3 s/12 s, 50 s 256 18 180 68.0 2 s/12 s, 50 s 256 19 175 65.2  2 s/12 s, 60 s 256 20 180 68.0  3 s/12s, 56 s 256

The mechanical properties of the expanded tubes were measured using amodified ASTM test with an Instron testing machine. The test specimenwas a ring or ribbon with four notches for hoop strength testing, whichwas cut from a blow molded tube that was expanded within a moldaccording to blow molding process of the present invention. The testingspecimen, illustrated in FIG. 7, had a 1 mm width, two two-sidednotches, and a 0.5 mm minimum area or distance between notches. Thetests were used to determine the ultimate apparent hoop strength, thestiffness or modulus in radial direction, and maximum elongation in theradial direction. The maximum elongation is a measure of the fracturetoughness of the samples.

The test method is a standard test method for apparent hoop tensilestrength for plastic or reinforced plastic pipe by a split disk method.Two mandrels, one fixed and one movable, were inserted through a testspecimen with the axis of the mandrel parallel to the axis of the testspecimen. During a test, the movable mandrel was moved at a constantspeed perpendicular to the axis of the mandrel which caused the testspecimen to deform. The mandrel was moved until one side of the testspecimen failed. The strain rate or the rate of movement of the movablemandrel is 0.2 in/min.

FIG. 8 shows exemplary force vs. displacement curves from tensiletesting as described above for tubes expanded with process condition No.3. The load is in units of lb_(f) and the displacement in units ofinches. The relatively linear portion of the curve between adisplacement of about 0.07 and 0.095 in represents yield or necking inthe sample, which is indicative of ductile behavior. The apparent hooptensile strength=13273 psi and hoop yield strength=9792.4 psi. Theradial elongation is 0.0234 in.

The crystallinity and Tg of the samples was determined from differentialscanning calorimetry. For the samples expanded with condition no. 3, thecrystallinity was 19.3% and the Tg=55.87° C.

FIG. 9 depicts a chart showing the measured apparent hoop ultimatetensile strength of test specimens, as described above, from PLLA tubesexpanded using process conditions in Table 1. FIG. 10 depicts a chartshowing the measured apparent hoop yield stress of the test specimens.FIG. 11 depicts a chart showing the measured maximum radial elongationof the test specimens.

The PLLA expanded tube samples were also subjected to axial elongationtests. In these tests the expanded tubes were stretched along the axialdirection. The strain rate along the axial direction was 1 in/min. FIG.12 depicts the axial elongation at break for tube samples at severalprocessing conditions from Table 1.

FIG. 13 depicts optical micrograph of a blow molded tube 250 that wasexpanded within a mold according to a blow molding process of thepresent invention. The optical micrograph is a image of the tube exposedto polarized light. The substantial homogeneity of the pattern along theaxis 256, particularly between arrows 252 and 254, illustrate theuniformity of structure and stress distribution along the axis resultingfrom the uniform expansion along the tube.

FIG. 14A depicts a close-up view of the optical micrograph of FIG. 13,further illustrating the uniformity of structure and stress. FIG. 14Bdepicts an optical micrograph of a blow molded tube expanded by a methodin which the entire tube is not expanded at the same time along itslength. The tube expands as a nozzle directing warm gas on the tubetranslates along the length of the tube. The optical micrograph in FIG.14B has irregular sets of patterns that illustrate structuralheterogeniety and a heterogeneous stress distribution.

FIGS. 15A-C illustrates heating of a heat sink with heating fluid andactive and passive cooling of the heat sink. Active cooling correspondsto cooling the heat sink with a cooling fluid flow. Passive coolingcorresponds to no cooling fluid fluid to the heat sink. The top graph isthe temperature (° C.) vs. time (sec) of the heat sink, the middle ispower input (watts) vs. time (sec) to the heat sink, and the bottomgraph is percent cooling water flow vs. time (sec) to the heat sink.There are two wave forms in each graph. The wave form on the leftcorresponds to active cooling and the wave form on the right correspondsto passive cooling.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

1. A method of making a stent comprising: heating an axial section of apolymer tube to facilitate radial deformation of the axial section;radially deforming the axial section of tube to a target diameter,wherein the axial section is radially deformed along its entire lengthat the same time; actively cooling the deformed axial section to below atarget temperature to stabilize the axial section at or close to thetarget diameter, wherein there is a cooling time delay between theradial deformation to the target diameter of the axial section and thestart of the active cooling, wherein the cooling time delay iscontrolled by a tension sensor that senses the tension in the axialsection radially or axially and the active cooling is activated when adesired tension is achieved; and fabricating a stent from the deformedaxial section after the cooling.
 2. The method of claim 1, wherein thepolymer is semicrystalline.
 3. The method of claim 1, further comprisingannealing the tube prior to radial deformation at a temperature thanallows formation of nuclei but that allows no or substantially nocrystal growth.
 4. The method of claim 1, wherein the axial section isdeformed at a temperature between 5-45 ° C. above a Tg of the tubepolymer.
 5. The method of claim 1, wherein the axial section is heatedto a target deformation temperature above the Tg of the polymer and theheated section is radially deformed at the target deformationtemperature.
 6. The method of claim 1, wherein the axial section isheated to a target deformation temperature and radially deformed afterreaching the target deformation temperature, wherein a time to heat theaxial section from Tambient to the target deformation temperature isbetween 5-20 s.
 7. The method of claim 1, wherein the heated axialsection is radially deformed immediately upon reaching a targetdeformation temperature.
 8. The method of claim 1, wherein the targettemperature is the Tg of the polymer or Tambient.
 9. The method of claim1, wherein the time to cool the axial section to below the targettemperature is less than 15 s.
 10. The method of claim 1, wherein thecooling comprises quenching the axial section below the targettemperature.
 11. The method of claim 1, further comprising axiallydeforming the prior to, during, or after radially deforming the polymer.12. A method of making a stent comprising: heating an axial section of apolymer tube disposed within a cylindrical mold to a deformationtemperature, wherein the heating facilitates radial deformation of theaxial section within the mold; increasing the pressure inside the axialsection of the mold to a pressure that radially deforms the axialsection; allowing the axial section to radially deform against an innersurface of the mold to a deformed diameter, wherein the axial section isradially deformed along its entire length at the same time; cooling thedeformed axial section below a target temperature to stabilize the axialsection at or close to the deformed diameter, wherein there is a coolingtime delay between the radial deforming of the axial section against theinner surface of the mold to the target diameter and the start of thecooling, wherein the cooling time delay is controlled by a tensionsensor that senses the tension in the axial section radially or axiallyand the cooling is activated when a desired tension is achieved; andfabricating a stent from the deformed axial section after the cooling.13. The method of claim 12, further comprising annealing the axialsection prior to heating to the deformation temperature, wherein atemperature of the axial section during the annealing is between Tg andTg +20 ° C.
 14. The method of claim 12, further comprising applyingtension along the cylindrical axis of the axial section to elongate theaxial section prior to, during, or after radially deforming the polymer.15. The method of claim 12, wherein the mold comprises a metal.
 16. Themethod of claim 12, wherein the mold is composed of a material having athermal conductivity greater than 50 W/m K.
 17. The method of claim 12,wherein the pressure is increased by blowing a gas into the axialsection.
 18. The method of claim 17, wherein the axial section is heatedby the gas, wherein the gas temperature is above the temperature atwhich the tube is radially deformed.
 19. The method of claim 17, whereinthe axial section is heated by electric elements on, in, or adjacent tothe mold; infra-red energy directed on the axial section; a warm gasdirected along the length of the axial section; or a combination of twoor more thereof.
 20. The method of claim 12, wherein the axial sectionis heated to the deformation temperature in 5-20 s.
 21. The method ofclaim 12, wherein the deformation temperature is between 5-45 ° C. abovea Tg of the tube polymer.
 22. The method of claim 12, wherein thedeformed axial section is cooled from the deformation temperature tobelow a Tg of the polymer in less than 15 s.
 23. The method of claim 12,wherein the deformed axial section is cooled by a heat sink adjacent tothe mold; a chilled liquid circulating in, on, or adjacent to the mold;a thermoelectric heat pump; a chilled gas directed into the deformedaxial section; a chilled gas directed onto the mold; or a combination oftwo or more thereof.
 24. The method of claim 12, wherein the moldsurface is porous to reduce or prevent entrapment of gas between anouter surface of the axial section and an inner surface of the mold.